The purpose of these studies is to understand the functional roles of neuroglia under physiological conditions as well as during nerve degeneration and regeneration following injury to the central nervous system. One goal is to study the membrane properties of glial cells which enable them to regulate the concentrations of ions and small molecules in the system of narrow intercellular clefts which constitutes the neuronal microenvironment. These homeostatic processes are vital to normal integrated nervous activity, and their failure is thought to play a role in the pathogenesis of epilepsy, migraine, intractable pain and brain edema. A second goal is to study the interactions between neurons and glial cells which result from nerve activity and to find out how these interactions are involved not only in the maintenance of normal function but also in the ability of the nervous system to regenerate following traumatic u=injury or stroke and to recover from autoimmune diseases such as multiple sclerosis. Glial cells will be studied under normal conditions and in various stages of axon degeneration and regeneration in the amphibian optic nerve as well as dissociated in tissue culture with or without neurons. Electrophysiological experiments are proposed using patch-clamp techniques to characterize ion conductances and chemical sensitivity of glial membranes and their regulation. Recent studies have shown that glial cells possess a variety of voltage-gated ion channels and chemical sensitivities of unknown functional significance whose expression appears related to the state of the cells. Their significance might be explained by studying the changes in their expression during axon degeneration and regeneration of the apposed axons. Histological methods will employ fluorescence, light and electron microscopy to describe neuroglial- neuronal relations. This proposal constitutes a multidisciplinary approach to understanding the properties of glial cells and neuron-glia interactions.